GSN synergies with actin-related transfer molecular chain to promote invasion and metastasis of HCC

Background Previous studies have shown that the ability of tumor cells to move and migrate is related to the molecular chain pathway mediated by actin. This study focused on the molecular mechanism of gelsolin (GSN) as an important actin-binding protein in promoting HCC invasion and metastasis. Methods The relationship between GSN expression and clinical characteristics was observed by immunohistochemistry (IHC). In vitro and in vivo experiments confirmed the role of GSN in HCC metastasis. Dual-immunoprecipitation (IP), immunofluorescence (IF), western blotting, and the gelatinase activity assay were used to investigate the mechanism of GSN-promoting metastasis. PEX fusion proteins were used to intervene in the transfer molecular chain. Results Our study found that GSN promoted HCC invasion and metastasis through its synergistic effect with actin-related transfer molecular chain (actin-CD44-MMPs). Concretely, as an important binding molecule of actin, GSN activated MMP2 by interacting with MMP14. Furthermore, CD44 might be a key node in the above-mentioned mechanism. The use of MMP14 domain (PEX fusion protein) to competitively bind to CD44 helped to inhibit the activation of downstream MMP2. Conclusions GSN played crucial roles in HCC metastatic process. An improved understanding of the multiple effects of GSN in HCC might facilitate a deeper appreciation of GSN as an important HCC regulator. The study identified GSN and its regulated transfer molecular chain as potential therapeutic targets for HCC (AU)

Markers of Stroma in Lung Cancer: Influence of COPD / Marcadores estromales en el cáncer de pulmón: la influencia de la enfermedad pulmonar obstructiva crónica

BACKGROUND: Stroma, mainly composed by fibroblasts, extracellular matrix (ECM) and vessels, may play a role in tumorigenesis and cancer progression. Chronic Obstructive Pulmonary Disease (COPD) is an independent risk factor for LC. We hypothesized that markers of fibroblasts, ECM and endothelial cells may differ in tumors of LC patients with/without COPD. METHODS: Markers of cultured cancer-associated fibroblasts and normal fibroblasts [CAFs and NFs, respectively, vimentin and alpha-smooth muscle actin (SMA) markers, immunofluorescence in cultured lung fibroblasts], ECM, and endothelial cells (type I collagen and CD31 markers, respectively, immunohistochemistry) were identified in lung tumor and non-tumor specimens (thoracotomy for lung tumor resection) from 15 LC-COPD patients and 15 LC-only patients. RESULTS: Numbers of CAFs significantly increased, while those of NFs significantly decreased in tumor samples compared to non-tumor specimens of both LC and LC-COPD patients. Endothelial cells (CD31) significantly decreased in tumor samples compared to non-tumor specimens only in LC patients. No significant differences were seen in levels of type I collagen in any samples or study groups. CONCLUSIONS: Vascular endothelial marker CD31 expression was reduced in tumors of non-COPD patients, while type I collagen levels did not differ between groups. A rise in CAFs levels was detected in lung tumors of patients irrespective of airway obstruction. Low levels of CD31 may have implications in the overall survival of LC patients, especially in those without underlying airway obstruction. Identification of CD31 role as a prognostic and therapeutic biomarker in lung tumors of patients with underlying respiratory diseases warrants attention

ANTECEDENTES: El estroma, compuesto principalmente por fibroblastos, matriz extracelular (MEC) y vasos, puede desempeñar un papel en la génesis tumoral y la progresión del cáncer. La enfermedad pulmonar obstructiva crónica (EPOC) es un factor de riesgo independiente para el carcinoma de pulmón (CP). Nuestra hipótesis fue que los marcadores de fibroblastos, MEC y células endoteliales pueden variar en los tumores de los pacientes con CP con o sin EPOC. MÉTODOS: Se identificaron los marcadores de fibroblastos asociados al cáncer y los fibroblastos normales cultivados (FAC y FN, respectivamente; marcadores: vimentina y α-actina del músculo liso [SMA por sus siglas en inglés]; inmunofluorescencia en fibroblastos de pulmón cultivados) y marcadores de la MEC y las células endoteliales (marcadores: colágeno tipo I y CD31, respectivamente; inmunohistoquímica) en muestras de pulmón tumoral y no tumoral (toracotomía para resección de tumores pulmonares) de 15 pacientes con EPOC-CP y 15 pacientes con solo CP. RESULTADOS: El número de FAC aumentó de forma significativa, mientras que el de FN disminuyó significativamente en las muestras tumorales en comparación con las muestras no tumorales de pacientes con CP y EPOC-CP. Las células endoteliales (CD31) disminuyeron también de forma significativa en las muestras tumorales en comparación con las muestras no tumorales solo en los pacientes con CP. No se observaron diferencias significativas en los niveles de colágeno tipo I en ninguna muestra o grupo de estudio. CONCLUSIONES: La expresión del marcador vascular endotelial CD31 se redujo en los tumores de los pacientes sin EPOC, mientras que los niveles de colágeno tipo I no difirieron entre los grupos. Se detectó un aumento en los niveles de FAC en los tumores de pulmón de los pacientes, con independencia de la presencia de obstrucción de las vías respiratorias. Los niveles bajos de CD31 pueden tener implicaciones en la supervivencia general de los pacientes con CP, en especial, en aquellos sin obstrucción subyacente de las vías respiratorias. Convendría estudiar e identificar el papel del CD31 como biomarcador terapéutico y de pronóstico en los tumores de pulmón de pacientes con enfermedades respiratorias subyacentes

Myofibroblasts and increased angiogenesis contribute to periapical cystic injury containment and repair

BACKGROUND: Myofibroblasts (MF) and angiogenesis are important factors in the development and expansion of cystic lesions, where these cells secrete growth factors and proteases, stimulating angiogenesis, matrix deposition and cell migration, affecting the growth of these periapicopathies. The present study aimed to evaluate the immunohistochemical expression of CD34 and Alpha-SMA in radicular cysts (RC) and residual radicular cysts (RRC), with the purpose of contributing to a better understanding of the expansion and progression of these periapical lesions. MATERIAL AND METHODS: The present study os a descriptive, quantitative and comparative analysis of positive CD34 and Alpha-SMA immunohistochemical expressions in 30 RC and 30 RRC specimens. Alpha-SMA expression was evaluated in the fibrous capsule of the lesions, at 100x magnification below the epithelial lining. A total of 10 higher immunostaining fields were selected and subsequently, positive cells were quantified at 400x magnification, averaged per field. Regarding the angiogenic index, immuno-labeled microvessel counts for the anti-CD34 antibody were performed in 10 fields at 200x magnification. RESULTS: Statistically significant differences regarding Alpha-SMA immunostaining were observed (p = 0.035), as well as a correlation between Alpha-SMA versus CD34 (p = 0.004) in RRC. However, the angiogenic index obtained by immunostaining for CD34 indicated no statistical difference between lesions. Intense inflammatory infiltrates were predominant in RC, while mild and moderate degrees were more commonly observed in RRC (p < 0.001). Intense inflammatory infiltrates were also more often noted in larger RRC (p = 0.041). Inflammatory infiltrates showed no significant correlation with α-SMA and CD34 immunostaining. CONCLUSIONS: The results indicate that the significant correlation found between the presence of MF and the angiogenic index are related to the repair process in RRC

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Nueva mutación en el gen ACTA2 (pMet84Val) en una familia con aneurismas de aorta familiares no sindrómicos / New mutation in the ACTA2 gene (pMet84Val) in a family with nonsyndromic familial aortic aneurysms

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Immunohistochemical analysis of cancer-associated fibroblasts and podoplanin in head and neck cancer

BACKGROUND: To immunohistochemically evaluate the association between the presence of cancer-associated fibroblasts (CAFs) and the tumour expression of podoplanin (PDPN) in head and neck squamous cell carcinoma (HNSCC) and their association with clinicopathological variables. MATERIAL AND METHODS: A tissue microarray (TMA) with biopsy sections from patients diagnosed with HNSCC was stained with antibodies against the CAFs marker, α-smooth muscle actin (α-SMA), and PDPN. We subsequently evaluated their expression to determine the association between them and with clinicopathological variables including age, primary tumour site, TNM stage, and tumour differentiation grade. RESULTS: Positive reaction to α-SMA was observed in the tumour stroma, revealing spindle-shaped cells compatible with CAFs, which showed a high expression in 62% of cases and a significant association with laryngeal carcinomas, advanced clinical stages, and lower tumour differentiation (P ≤ 0.05). PDPN staining on tumour cells showed low expression in 72% of cases, and it was not associated with any clinicopathological variable or with the presence of CAFs. CONCLUSIONS: The presence of CAFs in the tumour stroma is related to an aggressive phenotype and could increase as the disease progresses, although based on our findings, it would have no relationship, at least directly, with the expression of PDPN

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Actin allergen of common periwinkle sea snail (littorina littorea)

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Actin as a possible cross-reactive allergen between fish and poultry

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Amelioration of experimentally induced diabetic nephropathy and renal damage by nilotinib

Diabetes mellitus is an ever growing world-wide health problem. The patient has to stick to a firm life-long therapeutic regimen, otherwise diabetic complications will develop. Diabetic nephropathy (DN) is one of the most common diabetic complications and it requires careful medical attendance. Nilotinib hydrochloride is a protein tyrosine kinase inhibitor reported to have numerous therapeutic efficacies besides being an anticancer. In the current study, single I.P. streptozotocin (50 mg/kg) injection was used to induce type I diabetes mellitus in male Sprague–Dawley rats. After 8 weeks, significant deterioration of renal function with urinary excretion of nephrin, podocalyxin, and albumin was observed. Daily oral administration of nilotinib (20 mg/kg) for 8 weeks significantly improved signs of DN on all investigated scales. On a biochemical scale, kidney functions, albuminuria, urinary nephrin, podocalyxin excretion, and host oxidant/antioxidant balance significantly improved. Kidney content of nitric oxide, expression of toll-like receptors 4 and NF-káppaB/p65 activity significantly declined as well. On a histopathological scale, Alpha-smooth muscle actin and nestin expression significantly declined. Meanwhile, area of fibrosis significantly declined as seen with significant reduction in accumulation of extracellular matrix components and kidney content of collagen. Ultimately, such improvements were accompanied by significant restoration of normal kidney physiology and function. In conclusion, nilotinib can hinder progression of DN through various mechanisms. Reduction of oxidative stress, enhancement of host antioxidant defense system, reduction of inflammation, angiogenesis, tissue hypoxia, and pro-fibrogenic biomarker expression can be implicated in the beneficial therapeutic outcome observed with nilotinib therapy

Distribution of ki-67, alpha smooth muscle actin and vimentin in the reticulum and omasum of Baladi goat

Seven Baladi goats of both sexes (9 to 24 months old) were used to describe the distribution pattern of ki-67, alpha smooth muscle actin (áSMA) and vimentin (VIM) in the reticulum and omasum. This study was carried out using the avidin-biotin immunoperoxidase method. Ki-67 immunostaining was restricted to the basal cells layer in the epithelia of both the reticulum and omasum, suggesting the importance of ki-67 in epithelial cells proliferation and keratin biosynthesis. Immunostaining for áSMA was detected in smooth muscle cells in reticular folds, omasal lamiae and muscularis in both the reticulum and omasum, indicating the critical role of áSMA in muscular motility. The widespread distribution of VIM immunostainings in epithelia, fibroblasts in lamina propria and submucosa, and endothelia of blood vessels supports the importance of VIM as an intermediate filament protein. Detection of VIM in glial cells of enteric plexuses indicates its supportive role in the nervous control of both reticulum and omasum. Overall, this immunohistochemical study revealed non-significant differences in the expression of ki-67, áSMA, and VIM between the reticulum and omasum. This study thus verifies the important roles of ki-67, áSMA and VIM in the structure and function of the reticulum and omasum of Baladi goats

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Low-grade myofibroblastic sarcoma. Two rare tumors in two rare locations / Sarcoma miofibroblástico de bajo grado. Dos tumores infrecuentes en dos localizaciones poco habituales

Low-grade myofibroblastic sarcoma (LGMS) represents an atypical tumor composed of myofibroblasts with a predilection for the head and neck, especially in the tongue and oral cavity, with a high tendency to local recurrences and metastases, even after a long period. LGMS arising in the maxillary sinus and in the neck are extremely uncommon. To the best of our knowledge, only 50 cases of low-grade myofibroblastic sarcoma have been reported. We report two cases of LGMS of the maxillary sinus and neck, discussing clinical, histological, inmunohistochemical and therapeutic features (AU)

El sarcoma miofibroblástico de bajo grado (SMFBG) representa un tumor atípico, formado por miofibroblastos, que tiene predilección por cabeza y cuello, en especial la lengua y la cavidad oral, y se caracteriza por una elevada tendencia a las recidivas locales y a las metástasis, incluso después de transcurrido un período prolongado. Los SMFBG que se originan en el seno maxilar y en el cuello son excepcionales. Hasta lo que conocen los autores, solo se han publicado 50 casos de sarcoma miofibroblástico de bajo grado. Describimos 2 casos en los que se identificaron estos tumores, uno en el seno maxilar y el otro en el cuello, y abordamos sus características clínicas, histológicas, inmunohistoquímicas y terapéuticas (AU)

El trasfondo genético de la hipertrabeculación/miocardiopatía no compactada ventricular izquierda sigue sin estar claro / The genetic background of left ventricular hypertrabeculation / noncompaction remains vague

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El trasfondo genético de la hipertrabeculación/miocardiopatía no compactada ventricular izquierda sigue sin estar claro. Respuesta / The genetic background of left ventricular hypertrabeculation / noncompaction remains vague. Response

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Corrección en el artículo «Miocardiopatía no compactada familiar asociada con una mutación nueva en el gen de la alfa actina cardiaca», Rev Esp Cardiol. 2014; 67: 857-9 / Correction in article “Familial left ventricular 7noncompaction associated with a novel mutation in the alphacardiac actin gene”, Rev Esp Cardiol. 2014; 67: 857-9

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Escroto accesorio / Accessory scrotum

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Selección de genes de referencia en semen equino criopreservado para su uso en estudios de expresión genética con la técnica de PCR cuantitativa / Reference genes selection in cryopreserved equine semen for its use in studies of gene expression with the quantitative PCR technique

INTRODUCCIÓN: La gestión de bancos de germoplasma implica la conservación y uso de dosis seminales, pero también pueden ser una fuente de estudio sobre la calidad de los sementales y las propiedades del semen para su empleo post descongelación. Un criterio para medir la calidad seminal puede basarse en las diferencias de expresión de algunos genes implicados en la espermatogénesis y la maduración espermática. OBJETIVO: Análisis de genes expresados en semen equino criopreservado que ofrezcan una adecuada amplificación, especificidad y estabilidad para su empleo como genes de referencia en futuros estudios de expresión genética. MATERIAL Y MÉTODOS: Purificación de espermatozoides vivos mediante un gradiente de concentración discontinua a partir de pajuelas de semen criopreservado correspondiente a cuatro sementales. Extracción orgánica de ácidos ribonucleicos con tratamiento con la enzima desoxiribonucleasa y la amplificación selectiva de siete genes candidatos mediante retrotranscripción y reacción en cadena de la polimerasa en tiempo real en un solo paso. RESULTADOS: Tres de los genes seleccionados, β-Actina, Ubiquitina B y proteína Ribosomal L32 se amplifican correctamente. β-Actina, Ubiquitina B manifiestan la mayor estabilidad. CONCLUSIÓN: En los espermatozoides procedentes de muestras de semen criopreservado equino se puede detectar la presencia de ARNm, siendo el gen de la β-Actina y de la Ubiquitina B los más indicados como genes de referencia de los siete candidatos analizados

INTRODUCTION: The germoplasm bank management involves the conservation and use of semen doses, but can also be a source of study on the quality of stallions and semen properties for use after thawing. A criterion for measuring the semen quality may be based on differences in expression of some genes involved in spermatogenesis and sperm maturation. OBJECTIVE: Analysis of genes expressed in equine cryopreserved sperm that can provide adequate amplification, specificity and stability for use as future reference genes in gene expression studies. MATERIAL AND METHODS: Purification of live sperm through a discontinuous concentration gradient from cryopreserved semen straws corresponding to four stallions. Organic extraction of ribonucleic acids with deoxyribonuclease treatment and the selective amplification of seven candidate genes using a retrotranscription and a real time chain reaction of the polymerase in one step mode. Specificity is tested by melting curves and agarose gel electrophoresis. Also the stability of the genes is calculated. RESULTS: Three of the selected genes, β-actin, Ubiquitin B and Ribosomal protein L32 were properly amplified. β-Actin and Ubiquitin B showed the best stability. CONCLUSION: mRNA was amplified from equine cryopreserved semen samples, being the β-Actin and the Ubiquitin B genes the most suitable reference genes of the seven candidates analyzed

Selecting housekeepping genes as references for the normalization of quantitative PCR data in breast cancer

OBJECTIVE: The common reference genes of choice in relative gene expression studies based on quantitative real time polymerase chain reaction, ACTB and B2M, were shown to be regulated differently in respect to tissue type. In this study, the stability of the selected housekeeping genes for normalizing the qPCR data were identified in the tumor and its adjacent tissues in invasive breast cancer, and the variability of their levels according to the stages and the histopathologic subtypes was analyzed. METHODS: Four housekeeping genes: PUM1, RPL13A, B2M, and ACTB were analyzed in 99 surgically excised tissue specimens (50 tumor, 45 tumor adjacent and 4 normal breast tissues). Three of the most common softwares (GeNorm, NormFinder, and BestKeeper) were used for calculation purposes. RESULTS: When all of the tissue samples were included in analyses, PUM1 was the most stable gene according to calculations made with both NormFinder and BestKeeper; while PUM1/RPL13A combination was the most stable by GeNorm software. The PUM1 gene was also identified as the most stable gene among the four in all sample groups (in both Estrogen Receptor positive and Estrogen Receptor negative subgroups of invasive breast carcinoma and in normal breast tissue) according to calculations made using the NormFinder software. CONCLUSION: While suggesting PUM1 is one of the most stable single gene and the PUM1/RPL13A pair as one of the best housekeeping genes for the normalization of expression studies in invasive breast tumor studies, it will be more practical to evaluate stability once more and decide upon the reference gene accordingly within the sample group itself (AU)

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Modificación del comportamiento celular bajo el efecto de estatinas en células de pared arterial (I). Cambios en la dinámica celular / Alterations in cell behaviour under the effect of statins in arterial wall cells (I). Changes in cell dynamics

Los inhibidores de la 3-HMG-CoA-reductasa (estatinas) son fármacos cuyos beneficios clínicos en la prevención de las enfermedades cardiovasculares están ampliamente demostrados. Una parte de tales beneficios, y particularmente los que pueden tener lugar de forma más inmediata, se deben a efectos que pueden ser independientes del descenso de los niveles de colesterol y de cLDL. Estos efectos se conocen como efectos pleiotrópicos. En el presente trabajo, mediante cultivos de células implicadas en el proceso aterogénico -fibroblastos, monocitos, células endoteliales y células musculares lisas- sometidos a distintos tipos y dosis de estatinas, hemos intentado evidenciar los cambios en el comportamiento celular. Nuestros resultados apoyan la idea de que se producen cambios subsiguientes a la adición de las estatinas en el medio de cultivo, y que afectan tanto a la adhesividad celular como a la movilidad y -en el caso de las células musculares lisas- a la contractilidad. Estos cambios pueden explicar, al menos en parte, algunos de los efectos distintos a los directamente relacionados con el efecto hipocolesterolemiante. En el fondo de tales cambios se pueden encontrar modificaciones en el metabolismo intracelular (AU)

In the present study, using cultures of the cells involved in the atherogenic process: fibroblasts, monocytes, endothelial cells and smooth muscle cells submitted to different types and doses of statins, we have attempted to demonstrate the changes in cell behaviour. Our results support the idea that subsequent changes are produced on the addition of statins into the culture medium, and which affect cell adhesiveness, as well as mobility and. in the case of smooth muscle cells, the contractility. These changes may explain, at least partly, some of the effects other than those directly related to the lipid lowering effect. Behind such changes may be found alterations in intracellular metabolism.3-HMG-CoA-reductase inhibitors (statins) are drugs which have been widely demonstrated to have clinical benefits in the prevention of cardiovascular diseases. Some of these benefits, particularly those that may take place immediately, are due to effects that may be independent of the decrease in cholesterol and LDL-cholesterol levels. These effects are known as pleiotropic effects (AU)